Sørensen Karen Marie Juul, Meldgaard Theresa, Melchjorsen Connie Jenning, Fridriksdottir Agla J, Pedersen Henrik, Petersen Ole William, Kristensen Peter
Department of Engineering, Aarhus University, Gustav Wieds Vej 10, 8000 Aarhus C, Aarhus, Denmark.
Department of Cellular and Molecular Medicine, Centre for Biological Disease Analysis and Danish Stem Cell Centre, University of Copenhagen, Copenhagen, Denmark.
BMC Cancer. 2017 Jan 5;17(1):19. doi: 10.1186/s12885-016-2987-5.
One of the hallmarks of cancer is an altered energy metabolism, and here, mitochondria play a central role. Previous studies have indicated that some mitochondrial ribosomal proteins change their expression patterns upon transformation.
In this study, we have used the selection of recombinant antibody libraries displayed on the surface of filamentous bacteriophage as a proteomics discovery tool for the identification of breast cancer biomarkers. A small subpopulation of breast cells expressing both cytokeratin 19 and cytokeratin 14 was targeted using a novel selection procedure.
We identified the mitochondrial ribosomal protein s18a (Mrps18a) as a protein which is upregulated in breast cancer. However, Mrps18a was not homogeneously upregulated in all cancer cells, suggesting the existence of sub-populations within the tumor. The upregulation was not confined to cytokeratin 19 and cytokeratin 14 double positive cells.
This study illustrates how phage display can be applied towards the discovery of proteins which exhibit changes in their expression patterns. We identified the mitochondrial protein Mrps18a as being upregulated in human breast cancer cells compared to normal breast cells.
癌症的标志之一是能量代谢改变，线粒体在此过程中起着核心作用。先前的研究表明，一些线粒体核糖体蛋白在细胞转化时会改变其表达模式。
在本研究中，我们利用展示在丝状噬菌体表面的重组抗体文库筛选作为蛋白质组学发现工具，用于鉴定乳腺癌生物标志物。使用一种新颖的筛选程序靶向表达细胞角蛋白19和细胞角蛋白14的一小部分乳腺细胞。
我们鉴定出线粒体核糖体蛋白s18a（Mrps18a）在乳腺癌中表达上调。然而，Mrps18a并非在所有癌细胞中均呈均匀上调，这表明肿瘤内部存在亚群。这种上调并不局限于细胞角蛋白19和细胞角蛋白14双阳性细胞。
本研究说明了噬菌体展示如何应用于发现表达模式发生变化的蛋白质。我们鉴定出线粒体蛋白Mrps18a在人乳腺癌细胞中相对于正常乳腺细胞表达上调。
